Structural analysis of quazepam metabolites in bile by ion trap time-of-flight mass spectrometry
Structural analysis of quazepam metabolites in bile by ion trap time-of-flight mass spectrometry
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DOI：
10.1016/j.forsciint.2015.07.016
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发表时间：
2015-11-01
影响因子：
2.2
通讯作者：
Ohno, Youkichi
中科院分区：
文献类型：
--
作者：
Yamaguchi, Koji;Goda, Takahiro;Ohno, Youkichi
Quazepam （QZP）是一种长效苯二氮卓类催眠药。我们在胆汁中寻找新的QZP代谢物，并通过液相色谱-离子阱飞行时间质谱（LC-IT-TOF MS）测定其结构。代谢产物经b-葡萄糖醛酸酶处理后用乙酸乙酯提取。首先，获取单个质谱。其次，对含有一个氯原子的分子的同位素模式离子组成的峰进行了MSn谱分析。本研究发现的新型QZP代谢物为羟基西泮、羟基-甲氧基西泮、羟基-氧基西泮和羟基-甲氧基-氧基西泮，它们在氟苯基上有羟基和甲氧基；二羟基-氧基西泮和二羟基-甲氧基-氧基西泮，它们在七元环的3位上有一个羟基，另一个羟基和甲氧基在氟苯基上。我们证明LC-IT-TOF质谱是测定代谢物结构的有用工具。但是，不能确定氟苯基上羟基和甲氧基的确切位置。2015爱思唯尔爱尔兰有限公司版权所有。
Quazepam (QZP) is a long-acting benzodiazepine-type hypnotic. We searched for novel QZP metabolites in bile and determined their structures by liquid chromatography-ion trap time-of-flight mass spectrometry (LC-IT-TOF MS). The metabolites were extracted with ethyl acetate after b-glucuronidase treatment. First, a single MS spectrum was acquired. Second, MSn spectra were acquired for peaks that consisted of ions with the isotope pattern corresponding to molecules bearing one chlorine atom. The novel QZP metabolites found in this study were hydroxyquazepam, hydroxy-methoxyquazepam, hydroxy-oxoquazepam, and hydroxy-methoxy-oxoquazepam, which have the hydroxy and methoxy groups on the fluorophenyl group, and dihydroxy-oxoquazepam and dihydroxy-methoxy-oxoquazepam, which have one hydroxy group at the 3-position of the seven-membered ring and the other hydroxy group and the methoxy group on the fluorophenyl group. We demonstrated that LC-IT-TOF MS was a useful tool for determining the structure of the metabolites. However, the exact locations of the hydroxy and methoxy groups on the fluorophenyl group could not be identified. (C) 2015 Elsevier Ireland Ltd. All rights reserved.